Search

In recent years, artificial intelligence (AI), especially deep learning models, has increasingly been integrated into diagnosing and treating diabetic retinopathy (DR). From delving into the singular realm of ocular fundus photography to the gradual development of proteomics and other molecular approaches, from machine learning (ML) to deep learning (DL), the journey has seen a transition from a binary diagnosis of “presence or absence” to the capability of discerning the progression and severity of DR based on images from various stages of the disease course. Since the FDA approval of IDx-DR in 2018, a plethora of AI models has mushroomed, gradually gaining recognition through a myriad of clinical trials and validations. AI has greatly improved early DR detection, and we’re nearing the use of AI in telemedicine to tackle medical resource shortages and health inequities in various areas. This comprehensive review meticulously analyzes the literature and clinical trials of recent years, highlighting key AI models for DR diagnosis and treatment, including their theoretical bases, features, applicability, and addressing current challenges like bias, transparency, and ethics. It also presents a prospective outlook on the future development in this domain.

BackgroundOlder patients with advanced cholangiocarcinoma lack systemic therapy standards. These people have a high risk of chemotherapy, accompanied by adverse reactions and even discontinuation of treatment.Case presentationWe report a 78-year-old female subject with advanced intrahepatic cholangiocarcinoma presenting with unresectable lesions involving the hepatic veins, along with extensive metastatic lymph nodes. After the geriatric assessment, capecitabine was utilized for only one cycle owing to adverse events (AEs). Next, a combination of low-dose lenvatinib and tislelizumab was administrated as a second-line treatment, which resulted in remarkable early tumor shrinkage. The following individual lenvatinib taper enabled a manageable safety profile and durable deep response. A near-complete response was achieved, with the primary tumor significantly reducing from 5.6 cm × 4.7 cm to nearly complete disappearance, accompanied by complete regression of lymph nodes, and both progression-free survival and overall survival exceeding 24 months.ConclusionThe case provides valuable insights that could influence future treatment strategies for older patients with advanced cholangiocarcinoma who are unsuitable for chemotherapy. The dose-individualized chemotherapy-free regime of lenvatinib and tislelizumab might be used in similar cases to improve their outcomes.

IntroductionThe identification of risk factors for regional lymph node (r-LN) metastasis in rectal neuroendocrine tumors (R-NETs) remains challenging. Our objective was to investigate the risk factors associated with patients diagnosed with R-NETs exhibiting r-LN metastasis.MethodsPatient information was obtained from the Surveillance, Epidemiology, and End Results (SEER) database, complemented by data from the West China Hospital (WCH) databases. The construction cohort comprised patients diagnosed with R-NETs from the SEER database, while cases from the WCH database were utilized as the validation cohort. A novel nomogram was developed to predict the probability of r-LN metastasis, employing a logistic regression model.ResultsUnivariate analysis identified four independent risk factors associated with poor r-LN metastasis: age (HR = 1.027, p < 0.05), grade (HR = 0.010, p < 0.05), T stage (HR = 0.010, p < 0.05), and tumor size (HR = 0.005, p < 0.05). These factors were selected as predictors for nomogram construction.DiscussionThe novel nomogram serves as a reliable tool for predicting the risk of r-LN metastasis, providing clinicians with valuable assistance in identifying high-risk patients and tailoring individualized treatments.

Edamame (Glycine max (L.) Merr.), a specialty soybean prized for its nutritional value and taste, has witnessed a surge in demand within the U.S. However, subpar seedling stands have hindered its production potential, necessitating increased inputs for farmers. This study aims to uncover potential physiological factors contributing to low seedling emergence in edamame. We conducted comprehensive assessments on thirteen prominent edamame genotypes alongside two food-grade and two grain-type soybean genotypes, focusing on germination and emergence speed in both laboratory and field settings. Additionally, we employed single electrical conductivity tests and identified and quantified seed leachate components to distinguish among soybean types. Furthermore, using a LabField™ simulation table, we examined seed emergence across a wide soil temperature range (5°C to 45°C) for edamame and other soybean types. All seeds were produced under the same environmental conditions, harvested in Fall 2020, and stored under uniform conditions to minimize quality variations. Our findings revealed minimal divergence in emergence percentages among the seventeen genotypes, with over 95% germination and emergence in laboratory conditions and over 70% emergence in the field. Nonetheless, edamame genotypes typically exhibited slower germination speeds and higher leachate exudates containing higher soluble sugars and amino acids. Seed size did not significantly impact total emergence but was negatively correlated with germination and emergence speed, although this effect could be mitigated under complex field conditions. Furthermore, this study proposed differences that distinguish edamame from other soybean types regarding ideal and base temperatures, as well as thermal time. The finds offer valuable insights into edamame establishment, potentially paving the way for supporting local edamame production in the U.S.

The clam Cyclina sinensis is an economically important marine species in China. However, overfishing, habitat destruction, and inbreeding have led to the destruction of genetic resources. In this study, five natural populations [Dandong (DD), Dongying (DY), Tianjin (TJ), Wenzhou (WZ), and Yancheng (YC)] from different geographical locations were relocated and cultured homogeneously to study their potential for translocation and environmental adaptation by observing growth performance and nutrient content. There were significant differences in the growth rates of shell length (SL), shell height (SH), and shell width (SW) among the five populations (P

Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at an advanced stage, presenting limited therapeutic options and a grim prognosis due to its aggressive nature. Despite ongoing exploration of various combination therapies, a standardized treatment approach after the first-line treatment progress remains elusive. This report details the cases of two patients with unresectable advanced PDAC who underwent distinct conversion treatment regimens involving immune checkpoint inhibitors (ICIs). Remarkably, both patients became eligible for surgery following different anti-PD-1 antibody-based conversion therapies, ultimately achieving R0 resection. In essence, our findings highlight the efficacy of the anti-PD-1 antibody combined with a tyrosine kinase inhibitor (TKI) regimen and chemotherapy alongside anti-PD-1 antibody as viable conversion therapies for preoperative advanced PDAC. Tumor immune microenvironment (TIME) analysis underscores the intratumoral and intertumoral heterogeneity observed in the postoperative immune landscape of surgical specimens. This insight contributes to a deeper understanding of the potential benefits of these conversion therapies in addressing the challenging landscape of advanced PDAC.

BackgroundNeonatal-onset multisystem inflammatory disease (NOMID) is a rare and severe autoinflammatory disease caused by mutations of the NLRP3 gene and is characterized by a skin rash, fever, arthropathy, and neurologic manifestations. We herein report a neonatal case with recurrent rash, fever, and meningitis from 12 h after birth, and NOMID was diagnosed during the neonatal period. We also reviewed the clinical characteristics and genetic mutations of previously reported Chinese neonates with NOMID.Case presentation and literature reviewNOMID is rare in China, and there have been over 100 cases uncovered thus far, including ours. The patient we reported here was the youngest among the confirmed Chinese cases and had the de novo mutation c.1210G>C (p.V404L) in exon 4 of the NLRP3 gene, which has not been reported previously. All 25 patients manifested recurrent urticaria-like rash, and 24 were febrile. Of the 23 patients with genetic data available, all had NLRP3 mutations. The primary treatment of these patients entailed glucocorticoids and immunosuppressants; however, the IL-1 inhibitor was rarely used due to its current unavailability in China. One patient was cured by umbilical cord blood stem cell transplantation (UCBT), which provided an alternative treatment.ConclusionWe recommend that NOMID be considered for neonates with recurrent rash, fever, and aseptic meningitis. However, further research on underlying mechanisms and therapeutic regimens in China is necessary to provide improved management.

BackgroundSecreted frizzled-related proteins (SFRPs) were reported to be involved in cardiovascular diseases. This study aimed to observe plasma SFRP levels in acute aortic dissection (AD) patients and the effects of SFRP expression on AD prognosis.MethodsPlasma levels of SFRP1, SFRP2, SFRP3, SFRP4, and SFRP5 were measured in AD patients and non-AD (NAD) patients. The end-point events information of AD patients, including all-cause death and various clinical complications due to aortic dissection, was collected during a 36-month follow-up.ResultsThe SFRP1, SFRP2, SFRP3, and SFRP4 levels were increased in AD patients compared with those in NAD patients, while the SFRP5 concentrations were decreased. No differences in any of the SFRP levels were observed between the type A group and the type B group. The AD patients with end-point events exhibited higher SFRP1, SFRP2, SFRP3, and SFRP4 concentrations but lower SFRP5 levels than the patients without end-point events. In addition, the AD patients were divided into a high group and a low group based on the median SFRP levels, and Kaplan-Meier analysis revealed that the AD patients with high SFRP1, SFRP2, SFRP4, or SFRP5 levels had a better prognosis than those with low levels. However, the AD patients with high SFRP3 levels exhibited the opposite trends. The binary logistic regression analysis found that SFRP1, SFRP2, SFRP4, and SFRP5 were all negatively correlated with the occurrence of end-point events, while SFRP3 was positively correlated with its occurrence.ConclusionsSFRP levels are all changed in acute AD, which may affect the prognosis of AD patients. SFRPs may be a target to improve the prognosis of AD.

BackgroundAcute necrotizing encephalopathy (ANE) is a devastating neurologic condition that can arise following a variety of systemic infections, including influenza and SARS-Cov-2. The clinical features of COVID-19-associated ANE in pediatric patients based on multi-case data have not yet been described and remain obscure. We reviewed 12 pediatric patients to better describe the clinical features of ANE with COVID-19.MethodsWe retrospectively collected and summarized the clinical features of ANE in children with COVID-19. Clinical data were collected from 12 children, including their general status, clinical symptoms, laboratory tests, and neuroimaging features.ResultsAmong the subjects, 10 were over 5 years old and they accounted for 83.33%. A large percentage of those affected (66.67%) were females. The major manifestations included fever (100%), impaired consciousness (100%), and convulsions (75%). We determined that increased interleukin (IL)-6 and IL-10, and tumor necrosis factor-α and interferon gamma were not predictive of severe ANE and mortality in children with COVID-19 in this study. All children presented with abnormal neuroimaging with multiple and symmetrically distributed lesions, involving the thalamus, basal ganglia, cerebellum, and brain hemispheres. Eight of the 12 children died, resulting in a mortality rate of 66.67%, and 75% of these children were females. Importantly, we found the timely administration of mannitol after an acute onset of convulsions or disturbance of consciousness may be decreased the high mortality induced by ANE children with COVID-19.ConclusionCOVID-19 associated with ANE in children is characterized by sudden symptom onset, rapid disease progression, and high mortality.

ObjectivesThe current study aimed to investigate the pathogenesis of obesity-induced impaired bone mass accrual and the impact of dietary intervention on bone density in the mouse model of obesity.MethodsMice were fed with chow diet (CD) for 10 months, high-fat-diet (HFD) for 10 months, or HFD for 6 months then transferred to chow diet for 4 months (HFDt).ResultsWeight loss and decreased intrahepatic lipid accumulation were observed in mice following dietary intervention. Additionally, HFD feeding induced bone mass accrual, while diet intervention restrained trabecular bone density. These changes were further reflected by increased osteogenesis and decreased adipogenesis in HFDt mice compared to HFD mice. Furthermore, HFD feeding decreased the activity of the Wingless-related integration site (Wnt)-β-Catenin signaling pathway, while the Wnt signaling was augmented by diet intervention in the HFDt group.ConclusionsOur findings suggest that a HFD inhibits bone formation and that dietary intervention reverses this inhibition. Furthermore, the dietary intervention was able to compensate for the suppressed increase in bone mass to a level comparable to that in the CD group. Our study suggests that targeting the Wnt signaling pathway may be a potential approach to treat obesity-induced impaired bone mass accrual.

IntroductionLignification of fruit flesh is a common physiological disorder that occurs during post-harvest storage, resulting in the deterioration of fruit quality. Lignin deposition in loquat fruit flesh occurs due to chilling injury or senescence, at temperatures around 0°C or 20°C, respectively. Despite extensive research on the molecular mechanisms underlying chilling-induced lignification, the key genes responsible for the lignification process during senescence in loquat fruit remain unknown. MADS-box genes, an evolutionarily conserved transcription factor family, have been suggested to play a role in regulating senescence. However, it is still unclear whether MADS-box genes can regulate the lignin deposition that arises from fruit senescence.MethodsBoth senescence- and chilling-induced flesh lignification were simulated by applying temperature treatments on loquat fruits. The flesh lignin content during the storage was measured. Transcriptomic, quantitative reverse transcription PCR and correlation analysis were employed to identify key MADS-box genes that may be involved in flesh lignification. The Dual-luciferase assay was utilized to identify the potential interactions between MADS-box members and genes in phenylpropanoid pathway. Results and DiscussionThe lignin content of the flesh samples treated at 20°C or 0°C increased during storage, but at different rates. Results from transcriptome analysis, quantitative reverse transcription PCR, and correlation analysis led us to identify a senescence-specific MADS-box gene, EjAGL15, which correlated positively with the variation in lignin content of loquat fruit. Luciferase assay results confirmed that EjAGL15 activated multiple lignin biosynthesis-related genes. Our findings suggest that EjAGL15 functions as a positive regulator of senescence-induced flesh lignification in loquat fruit.

Background & aimsThe effect of change in non-alcoholic fatty liver disease (NAFLD) status on incident diabetes has not been well studied. We aimed to investigate the association of NAFLD development and remission with the risk of incident diabetes during a median of 3.5-year follow-up.MethodsA total of 2690 participants without diabetes were recruited in 2011-2012 and assessed for incident diabetes in 2014. Abdominal ultrasonography was used to determine the change of NAFLD. 75 g oral glucose tolerance test (OGTT) was performed to determine diabetes. NAFLD severity was assessed using Gholam’s model. The odds ratios (ORs) for incident diabetes were estimated by logistic regression models.ResultsNAFLD was developed in 580 (33.2%) participants and NAFLD remission occurred in 150 (15.9%) participants during a median of 3.5-year follow-up. A total of 484 participants developed diabetes during follow-up, including 170 (14.6%) in consistent non-NAFLD group, 111 (19.1%) in NAFLD developed group, 19 (12.7%) in NAFLD remission group, and 184 (23.2%) in sustained NAFLD group. The development of NAFLD increased the risk of incident diabetes by 43% (OR, 1.43; 95%CI, 1.10-1.86) after adjustment for multiple confounders. Compared with sustained NAFLD group, remission of NAFLD reduced the risk of incident diabetes by 52% (OR, 0.48; 95%CI, 0.29-0.80). The effect of NAFLD alteration on incident diabetes was not changed after adjustment for body mass index or waist circumference, change of body mass index or waist circumference. In NAFLD remission group, participants with non-alcoholic steatohepatitis (NASH) at baseline were more likely to develop diabetes (OR, 3.03; 95%CI, 1.01-9.12).ConclusionsNAFLD development increases the risk of incident diabetes, whereas NAFLD remission reduces the risk of incident diabetes. Moreover, presence of NASH at baseline could attenuate the protective effect of NAFLD remission on incident diabetes. Our study suggests that early intervention of NAFLD and maintenance of non-NAFLD are important for prevention of diabetes.

BackgroundAlthough dexmedetomidine (DEX) is widely used during the perioperative period in patients with hepatocellular carcinoma (HCC), its clinical effects on liver function and postoperative inflammation are unclear. This study aimed to explore effects of DEX on postoperative liver function and inflammation in patients with HCC after hepatectomy.MethodsA retrospective cohort study with propensity score matching was performed. A total of 494 patients who underwent hepatectomy from June 2019 to July 2020 and fulfilled the eligibility criteria were included in this study. Baseline data, liver function indexes and inflammation-related biomarkers were collected and compared between the two groups. Survival analysis was conducted to investigate the effects of DEX on the overall survival (OS) of patients. Propensity score matching (PSM) was used to minimize bias between the two groups.ResultsThe study cohort comprised 189 patients in the DEX-free group and 305 patients in the DEX group. Patients in the DEX group had lower levels of alanine transaminase (ALT, P = 0.018) and lactate dehydrogenase (LDH, P = 0.046) and higher level of serum albumin (ALB, P < 0.001) than patients in the DEX-free group before discharge. A total of 107 pairs of patients were successfully matched by PSM. Results consistently suggested that ALT and LDH levels were significantly lower (P = 0.044 and P = 0.046, respectively) and ALB levels were significantly higher (P = 0.002) in the DEX group than in the DEX-free group in the early postoperative period. No significant differences of inflammation-related biomarkers were observed between two groups after PSM. Neither the Kaplan–Meier survival analysis nor the multiple Cox regression survival analysis identified DEX as a contributing factor that would affect the OS of patients after PSM.ConclusionDEX exerts protective effects on liver function while has little effects on inflammation-related biomarkers in the early postoperative period in patients undergoing hepatectomy due to HCC.

Although small cell neuroendocrine carcinoma of the ureter (ureteral SCNEC) is rare, it always leads to a poor prognosis. Also, no treatment recommendation has been given for ureteral SCNEC, with only PD-1/PD-L1 inhibitors being used for its treatment. Here, we report a case of atypical symptoms of cardiac infarction caused by a PD-1 inhibitor used in the treatment of ureteral SCNEC and hope to address concerns regarding the possible cardiac toxicity caused by PD-1/PD-L1 inhibitors in ureteral SCNEC patients.

Despite an increasing appreciation of the importance of host–microbe interaction in healthy growth, information on gut microbiota changes of the Chinese giant salamander (Andrias davidianus) during growth is still lacking. Moreover, it is interesting to identify gut microbial structure for further monitoring A. davidianus health. This study explored the composition and functional characteristics of gut bacteria in different growth periods, including tadpole stage (ADT), gills internalization stage (ADG), 1 year age (ADY), 2 year age (ADE), and 3 year age (ADS), using high-throughput sequencing. The results showed that significant differences were observed in microbial community composition and abundance among different growth groups. The diversity and abundance of intestinal flora gradually reduced from larvae to adult stages. Overall, the gut microbial communities were mainly composed of Fusobacteriota, Firmicutes, Bacteroidota, and Proteobacteria. More specifically, the Cetobacterium genus was the most dominant, followed by Lactobacillus and Candidatus Amphibiichlamydia. Interestingly, Candidatus Amphibiichlamydia, a special species related to amphibian diseases, could be a promising indicator for healthy monitoring during A. davidianus growth. These results could be an important reference for future research on the relationship between the host and microbiota and also provide basic data for the artificial feeding of A. davidianus.

ObjectiveSelenium (Se) is an essential trace element and may affect cervical cancer occurrence and progression. The association between selenium supplementation and acute toxic reactions and clinical outcomes in patients with locally advanced cervical cancer treated with concurrent chemoradiotherapy remains unclear. The aim of this study was to determine the safety profile of add-on Se yeast and assess the potential of Se to ameliorate the hematologic toxicity of concurrent chemoradiotherapy in patients with cervical cancer.MethodsPatients with Federation International of Gynecology and Obstetrics (FIGO) stage IIB cervical cancer who met all inclusion criteria were randomly assigned to either the experimental group or the control group. The experimental group received Se yeast tablets (100 μg Se, twice daily), while the control group received placebos (twice daily) for 5 weeks in total. All patients in both groups received standard treatment, including pelvic external irradiation, concurrent five cycles of chemotherapy, and brachytherapy. Measures included the incidence of myelosuppression, impairment of liver and kidney function, objective response rate (ORR), and blood Se concentrations before, during and after the treatment of the two groups.ResultsA total of 104 eligible patients were enrolled in the experimental group (n = 50) or the control group (n = 54). The ORR in the experimental group and control group were 96 and 94%, respectively (p = 0.47). The baseline levels of blood Se before treatment in the experimental and control groups were similar (58.34 ± 17.63 μg/L and 60.21 ± 18.42 μg/L, p = 0.60), but the concentrations became significantly different after course completion between the two groups (76.16 ± 24.47 μg/L and 57.48 ± 14.92 μg/L, respectively, p

Cancer is a major medical problem worldwide. Due to its high heterogeneity, the use of the same drugs or surgical methods in patients with the same tumor may have different curative effects, leading to the need for more accurate treatment methods for tumors and personalized treatments for patients. The precise treatment of tumors is essential, which renders obtaining an in-depth understanding of the changes that tumors undergo urgent, including changes in their genes, proteins and cancer cell phenotypes, in order to develop targeted treatment strategies for patients. Artificial intelligence (AI) based on big data can extract the hidden patterns, important information, and corresponding knowledge behind the enormous amount of data. For example, the ML and deep learning of subsets of AI can be used to mine the deep-level information in genomics, transcriptomics, proteomics, radiomics, digital pathological images, and other data, which can make clinicians synthetically and comprehensively understand tumors. In addition, AI can find new biomarkers from data to assist tumor screening, detection, diagnosis, treatment and prognosis prediction, so as to providing the best treatment for individual patients and improving their clinical outcomes.

Phosphatidylinositol-4-kinase alpha (PI4KIIIα), encoded by the PI4KA gene, can synthesize phosphatidylinositol-4-phosphate (PI-4-P), which serves as a specific membrane marker and is instrumental in signal transduction. PI4KA mutations can cause autosomal recessive diseases involving neurological, intestinal, and immunological conditions (OMIM:619621, 616531, 619708). We detected sepsis, severe diarrhea, and decreased immunoglobulin levels in one neonate. Two novel compound heterozygous mutations, c.5846T>C (p.Leu1949Pro) and c.3453C>T (p.Gly1151=), were identified in the neonate from the father and the mother, respectively. Sanger sequencing and reverse transcription polymerase chain reaction (RT-PCR) for peripheral blood and minigene splicing assays showed a deletion of five bases (GTGAG) with the c.3453C>T variant at the mRNA level, which could result in a truncated protein (p.Gly1151GlyfsTer17). The missense mutation c.5846T>C (p.Leu1949Pro) kinase activity was measured, and little or no catalytic activity was detected. According to the clinical characteristics and gene mutations with functional verification, our pediatricians diagnosed the child with a combined immunodeficiency and intestinal disorder close to gastrointestinal defects and immunodeficiency syndrome 2 (GIDID2; OMIM: 619708). Medicines such as immunomodulators are prescribed to balance immune dysregulation. This study is the first report of a synonymous mutation in the PI4KA gene that influences alternative splicing. Our findings expand the mutation spectrum leading to PI4KIIIa deficiency-related diseases and provide exact information for genetic counseling.

Sleep has been related to a variety of health outcomes. However, no association between sleep and asthenozoospermia has been reported. The aim of this study is to first investigate the relationship between sleep status and asthenozoospermia risk. A case-control study, including 540 asthenozoospermia cases and 579 controls, was performed from June 2020 to December 2020 in the infertility clinic from Shengjing Hospital of China Medical University. Data on sleep status were collected by Pittsburgh sleep quality index questionnaires and asthenozoospermia was diagnosed based on the World Health Organization guidelines. Odds ratio (OR) with 95% confidence interval (95% CI) was calculated by logistic regression analysis to assess the aforementioned association. Results of this study demonstrated that compared with total sleep duration of 8–9 h/day, < 8 h/day was related to asthenozoospermia risk (OR: 1.44, 95% CI: 1.05–1.99); compared to good sleep quality, poor sleep quality was associated with asthenozoospermia risk (OR: 1.35; 95% CI: 1.04–1.77). There were multiplicative model interaction effects between sleep quality and tea drinking (p = 0.04), rotating night shift work (p < 0.01) on asthenozoospermia risk. However, we failed to detect any associations between night sleep duration, daytime napping duration, night bedtime, wake-up time, sleep pattern and asthenozoospermia risk. In conclusion, short total sleep duration and poor sleep quality might be related to asthenozoospermia risk. Further well-designed prospective studies are warranted to confirm our findings.

The poultry red mite Dermanyssus gallinae is an economically important pest in poultry farms worldwide, but an effective treatment option is lacking. The current study determined the effectiveness of six Chinese herbal medicines [Syzygium aromaticum (clove), Hibiscus syriacus (Hibiscus), Illicium verum (star anise), Leonurus artemisia (motherwort), Cinnamomum cassia (cinnamon), and Taraxacum sp. (dandelion)] against D. gallinae. Alcohol extracts were prepared via the solvent extraction method and the phenol, flavonoid, and tannin contents were determined. These active components were highest in S. aromaticum and lowest in H. syriacus, I. verum. No tannin content was detected in L. artemisia. All extracts showed contact toxicity against D. gallinae at a test concentration of 1 g/mL, with S. aromaticum and L. artemisia resulting in 100% mortality. S. aromaticum, L. artemisia, and I. verum showed the best efficacy (LC50 0.159, 0.200, and 0.292 g/mL, respectively). Different combinations of extracts showed an additive effect of I. verum LC90 + L. artemisia LC90. The acaricidal efficacy of this combination was tested against different developmental stages of D. gallinae, being most efficacious against nymphal and larval D. gallinae, with a corrected mortality rate of 100%. However, inhibition of egg hatching was only 53.69%. Taken together, these results highlight I. verum LC90 + L. artemisia LC90 as a promising compound with severe contact toxicity against D. gallinae. Given the wide cultivation of these species and their extensive use in foodstuffs and cosmetics as flavors and fragrances, they could be a cheap, readily available ecofriendly alternative to pesticides currently used in poultry farms.

Cadmium (Cd2+) and mercury ions (Hg2+) are essential for the quality control of food samples because of their serious toxicity to human health, but the effective and simple strategy for their parallel detection remains challenging. In this paper, a rapid and simple parallel detection method for Cd2+ and Hg2+ was developed using carbon dots (CDs) as fluorescent sensors. A one-step hydrothermal method with a single precursor l-arginine as both the carbon and nitrogen sources was employed to prepare nitrogen-doped CDs (N-CDs). N-CDs exhibited a uniform particle size and excitation-independent fluorescence emission. The maximum emission wavelength of N-CDs was observed at 354 nm with the excitation wavelength at 295 nm. The quantum yield of N-CDs reached as high as 71.6% in water. By using sodium diphosphate and phytic acid as masking agents, the fluorescent sensor can be quenched by Cd2+ and Hg2+ in the linear range of 0–26.8 μM and 0–49.9 μM within 5 min. Other common ions in farm products showed no significant effect on the fluorescence intensity of the sensing system. The results demonstrated that the sensing system had good selectivity and sensitivity for Cd2+ and Hg2+. The detection limits for Cd2+ and Hg2+ were 0.20 and 0.188 μM, respectively. In addition, the fluorescent sensor had been successfully applied for the detection of Cd2+ and Hg2+ in fruits and vegetables, and the recoveries were 86.44–109.40% and 86.62–115.32%, respectively. The proposed fluorescent sensor provides a rapid, simple, and sensitive detection method for Cd2+ and Hg2+ in food samples and thus a novel quantitative detection method for heavy metal ions in foods.

Emerging evidence suggests that gut microbiota, short-chain fatty acids (SCFAs), and inflammatory cytokines play important roles in the pathogenesis of diabetic cognitive impairment (DCI). However, little is known about alterations of gut microbiota and SCFA levels as well as the relationships between inflammatory cytokines and cognitive function in Chinese DCI patients. Herein, the differences in the gut microbiota, plasma SCFAs, and inflammatory cytokines in DCI patients and type 2 diabetes mellitus (T2DM) patients were explored. A cross-sectional study of 30 DCI patients and 30 T2DM patients without mild cognitive impairment (MCI) was conducted in Tianjin city, China. The gut microbiota, plasma SCFAs, and inflammatory cytokines were determined using 16S ribosomal RNA (rRNA) gene sequencing, gas chromatography-mass spectrometry (GC-MS), and Luminex immunofluorescence assays, respectively. In addition, the correlation between gut microbiota and DCI clinical characteristics, SCFAs, and inflammatory cytokines was investigated. According to the results, at the genus level, DCI patients presented a greater abundance of Gemmiger, Bacteroides, Roseburia, Prevotella, and Bifidobacterium and a poorer abundance of Escherichia and Akkermansia than T2DM patients. The plasma concentrations of acetic acid, propionic acid, isobutyric acid, and butyric acid plummeted in DCI patients compared to those in T2DM patients. TNF-α and IL-8 concentrations in plasma were significantly higher in DCI patients than in T2DM patients. Moreover, the concentrations of acetic acid, propionic acid, butyric acid, and isovaleric acid in plasma were negatively correlated with TNF-α, while those of acetic acid and butyric acid were negatively correlated with IL-8. Furthermore, the abundance of the genus Alloprevotella was negatively correlated with butyric acid, while that of Holdemanella was negatively correlated with propanoic acid and isobutyric acid. Fusobacterium abundance was negatively correlated with propanoic acid. Clostridium XlVb abundance was negatively correlated with TNF-α, while Shuttleworthia abundance was positively correlated with TNF-α. It was demonstrated that the gut microbiota alterations were accompanied by a change in SCFAs and inflammatory cytokines in DCI in Chinese patients, potentially causing DCI development. These findings might help to identify more effective microbiota-based therapies for DCI in the future.

Immune-related myocarditis is a severe and even life-threatening immune-related adverse event (irAE) which may also be underestimated due to the challenge in diagnosis. The inherent difference between individuals with immune-associated myocarditis has received little attention. Our study aimed to identify which baseline characteristics could contribute to distinguishing mild from severe ICI myocarditis. A retrospective analysis was conducted between March 2019 and June 2020 in West China Hospital, and 18 patients with immune-related myocarditis were studied. Patients were classified as having mild (n = 12) or severe myocarditis (n = 6), according to the clinical manifestations and hemodynamic complications. Factors associated with severe myocarditis were identified by comparing covariates derived from medical records in various groups. In this retrospective analysis, the median age of the 18 patients was 60 years old. Most myocarditis cases occur early and approximately after the first or second ICI infusion. The severity of myocarditis may be correlated with lactate dehydrogenase (LDH) (p = 0.04) and troponin levels (p = 0.0057). The relationship between troponin and myocarditis was further confirmed in another cohort, which included 30 patients. In addition, patients are more likely to develop multi-irAEs, and myositis was the most common second irAE. Those who experience multi-irAEs usually had significantly higher LDH (p = 0.02) and myoglobin levels (p = 0.02) than those who did not experience them. All patients were treated with steroids timely, and the mortality rate was 5.6% in our study. In this study, we explored risk factors for severe myocarditis and emphasized the importance of a multidisciplinary team in assisting diagnosis and treatment options. It is critical to initiate corticosteroid therapy, regardless of the severity of the myocarditis.

Single-cell RNA sequencing (scRNA-seq) provides high-resolution information on transcriptomic changes at the single-cell level, which is of great significance for distinguishing cell subtypes, identifying stem cell differentiation processes, and identifying targets for disease treatment. In recent years, emerging single-cell RNA sequencing technologies have been used to make breakthroughs regarding decoding developmental trajectories, phenotypic transitions, and cellular interactions in the cardiovascular system, providing new insights into cardiovascular disease. This paper reviews the technical processes of single-cell RNA sequencing and the latest progress based on single-cell RNA sequencing in the field of cardiovascular system research, compares single-cell RNA sequencing with other single-cell technologies, and summarizes the extended applications and advantages and disadvantages of single-cell RNA sequencing. Finally, the prospects for applying single-cell RNA sequencing in the field of cardiovascular research are discussed.

Objective: The purpose of this study was to investigate the relationship between GSDMB gene polymorphism and genetic susceptibility to cervical cancer in the Han population in Northeast China.Methods: In this case–control study, the genotypes and alleles of rs8067378 in the GSDMB gene were analyzed by multiplex polymerase chain reaction (PCR) and next-generation sequencing methods in 482 cervical cancer (CC) patients, 775 cervical squamous intraepithelial lesion (SIL) patients, and 495 healthy women. The potential relationships between the SNP of the GSDMB gene with SIL and CC were analyzed by multivariate logistic regression analysis combined with 10,000 permutation tests.Results: In the comparison between the SIL group and the control group, the genotype and allele distribution frequencies of rs8067378 SNP of the GSDMB gene were statistically significant (p = 0.0493 and p = 0.0202, respectively). The allele distribution frequencies of rs8067378 were also statistically significant in the comparison between high-grade cervical squamous intraepithelial lesion (HSIL) and low-grade cervical squamous intraepithelial lesion (LSIL) groups with control group ( p = 0.0483 and p = 0.0330, respectively). Logistic regression analysis showed that after adjusting for age, the rs8067378 SNP of the GSDMB gene was significantly associated with the reduced risk of SIL under the dominant model (p = 0.0213, OR = 0.764, CI = 0.607–0.961) and the additive model (p = 0.0199, OR = 0.814, and CI = 0.684–0.968), and its mutant gene G may play a role in the progression of healthy people to LSIL and even HSIL as a protective factor. However, there was no significant association between cervical cancer and its subtypes with the control group (p > 0.05). After 10,000 permutations, there was still no correlation that has provided evidence for the accuracy of our study.Conclusion: The results of this study showed that rs8067378 single nucleotide polymorphism of the GSDMB gene may reduce the risk of SIL and protect the susceptibility to cervical precancerous lesions in the Northeast Chinese Han population, but it has no significant correlation with the progression of cervical cancer.

Dissolved organic carbon (DOC) is the main participant in carbon cycles through water pathways. Recent studies have highlighted the roles of aquatic systems in landscape and watershed carbon budgets. This study is based on 261 samples collected between 2016 and 2017, from individual water types (e.g., river/stream, lake/pond, icing/spring, snow/rain, groundwater/ice, and others) in the source area of the Yellow River (SAYR). These samples were analyzed for examining the distributive features of DOC in aquatic systems, especially in relation to environmental factors. It shows that: 1) DOC concentrations in permafrost-related waters (7.2–234.4 mg C·L−1) were often the highest among all aquatic DOC sources (lakes/ponds: 21.3 ± 34.1 mg C·L−1, rivers/streams: 4.3 ± 3.7 mg C·L−1, and groundwater: 1.8 ± 1.4 mg C·L−1); 2) the seasonality of riverine DOC showed declining features in 2016 and high in summer/autumn, followed by a spring freshet in 2017, and a close association with intra-annual precipitation modes; 3) the main controls of aquatic DOC are permafrost presence, precipitation, and NDVI, and they contribute to 38% of variances of environmental variables in affecting variations in aquatic DOC in the SAYR; and 4) a literature review on biodegradable DOC (BDOC) of varied aquatic DOC pools indicates the highest DOC concentrations (48–1,548 mg C·L−1) and BDOC (23–71%) of ground-ice meltwater. Thus, we suggest that in the SAYR, permafrost dynamics dominate aquatic DOC distribution, and permafrost thaw may alter aquatic DOC budgets, eventually becoming an additional source for atmospheric carbon emissions.

Cervical cancer (CC) is one of the main malignant tumors that threaten the health and lives of women around the world, and its morbidity and mortality rate ranks fourth. At present, most studies on the genetic background of CC focus on genetic polymorphisms. Single nucleotide polymorphisms (SNPs) are considered clinically as potential diagnostic and therapeutic biomarkers for a variety of tumors. Therefore, we aimed to explore the association between SNPs in different genes (EXOC1 gene, BCL2 gene, CCAT2 gene and CARD8 gene) and susceptibility to CC. This study is a case-control study based on women in northern Chinese, which included 492 women with CC and 510 healthy women. This study used multiplex PCR combined with next-generation sequencing to genotype the selected SNPs (rs13117307(C/T) in EXOC1 gene, rs2279115(C/A) in BCL2 gene, rs6983267(G/T) in CCAT2 gene and rs7248320(G/A) in CARD8 gene). The results of the study showed that there was no significant association between the four SNPs and the susceptibility to CC. However, in further stratified analysis, we found that rs13117307 and rs2279115 were significantly related to squamous cell carcinoma antigen (SCC-Ag) levels in women with CC, and rs6983267 was significantly related to the menopausal status of women with CC. Specifically, alleles T of rs13117307 and genoytpe AA of rs2279115 when SCC-Ag is greater than 1.5 ng/ml increase the risk of CC. The genotype TG/TG+TT of rs6983267 increases the risk of CC in premenopausal women. In conclusion, although we did not directly find a significant correlation between four SNPs, rs13117307 in EXOC1 gene,rs2279115 in BCL2 gene, rs6983267 in CCAT2 gene and rs7248320 in CARD8 gene, and CC susceptibility, we found that SNPs rs13117307, rs2279115, rs6983267 were associated with the clinical characteristics of several patients' CC patients. Therefore, this study provides us with new ideas for understanding CC and the diagnosis and treatment of CC in the future.

Background and ObjectivesZeaxanthin (ZEA) as one of the biologically active phytochemicals presents a neuroprotective effect. Since ZEA may play its anti-oxidative role in neurodegenerative diseases including Alzheimer’s disease (AD), we hypothesized cognitive defects could be prevented or deferred by ZEA pre-treatment.Methods and Study DesignAll the rats were randomly divided into four groups (control, Aβ1–42, ZEA, and ZEA + Aβ groups). Learning and memory ability of rats, cerebrovascular ultrastructure changes, the redox state, endothelin-1 (ET-1) level, and amyloid-β peptide (Aβ) level in plasma and the Aβ transport receptors which are advanced glycation end products (RAGEs) and LDL receptor-related protein-1 (LRP-1) and interleukin-1β (IL-1β) expressions in the cerebrovascular tissue were measured in the present study.ResultsThe escape latency and frequency of spanning the position of platform showed significant differences between the Aβ group and ZEA treatment groups. ZEA could prevent the ultrastructure changes of cerebrovascular tissue. In addition, ZEA also showed the protective effects on regulating redox state, restraining ET-1 levels, and maintaining Aβ homeostasis in plasma and cerebrovascular. Moreover, the disordered expressions of RAGE and LRP-1 and IL-1β induced by Aβ1–42 could be prevented by the pre-treatment of ZEA.ConclusionZEA pre-treatment could prevent learning and memory impairment of rats induced by Aβ1–42. This neuroprotective effect might be attributable to the anti-oxidative and anti-inflammatory effects of ZEA on maintaining the redox state and reducing the Aβ level through regulating the Aβ transport receptors and inflammatory cytokine of the cerebrovascular tissue.

α-Glucosidase is a potent drug target for treating type II diabetes mellitus. A great number of α-glucosidase inhibitors have been developed based on the molecular skeletons of bioactive natural products. However, efficient fluorescent probes for α-glucosidase detection are still limited, not to mention the probes with additional inhibitory functions. In this work, aiming for the enzyme’s highly specific detection, we designed and synthesized two environmentally sensitive fluorescent probes, namely, LD01 and LD02, respectively, based on conjugates of coumarin and cinnamic acid derivatives. We found a significant responsive emission enhancement upon LD02’s binding to α-glucosidase. These newly designed probes can act as a simple but efficient tool to evaluate the binding affinity of α-glucosidase to their inhibitors.

Teaching has long been considered as one of the most challenging professions worldwide due to the involvement of numerous linguistic, socio-political, social, and psych-emotional factors. Because of these factors, english as a foreign language (EFL) teachers are psychologically, emotionally, and physically pressed in their job. These damaging pressures often result in negative academic outcomes for teachers, students, and educational systems. Despite dire consequences, few studies (if any) have examined the role of psycho-emotional factors in improving teaching performance and reducing negative emotions at the workplace. To fill this gap, this mini-review article aimed to present a theoretical analysis of three constructs of occupational adjustment, psychological hardiness, and burnout. In so doing, the definitions, conceptualizations, dimensions, and empirical studies related to each variable were presented. The study ends with the existing research gaps and offers some implications for EFL teachers and other stakeholders by increasing their knowledge of emotions in occupational environments and the consequences that such emotions can have for an organization.

Background and aims: As a major cause of liver disease worldwide, non-alcoholic fatty liver disease (NAFLD) comprises non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). Due to the high prevalence and poor prognosis of NASH, it is critical to understand its mechanisms. However, the etiology and mechanisms remain largely unknown. In addition, the gold standard for the diagnosis of NASH is liver biopsy, which is an invasive procedure. Therefore, there is a pressing need to develop noninvasive tests for NASH diagnosis. The goal of the study is to discover key genes involved in NASH development and investigate their value as noninvasive biomarkers.Methods: The Gene Expression Omnibus (GEO) database was used to obtain two datasets encompassing NASH patients and healthy controls. We used weighted gene co-expression network analysis (WGCNA) and differential expression analysis in order to investigate the association between gene sets and clinical features, as well as to discover co-expression modules. A protein-protein interaction (PPI) network was created to extract hub genes. The results were validated using another publicly available dataset and mice treated with a high-fat diet (HFD) and carbon tetrachloride (CCl4).Results: A total of 24 differentially co-expressed genes were selected by WGCNA and differential expression analysis. KEGG analysis indicated most of them were enriched in the focal adhesion pathway. GO analysis showed these genes were mainly enriched in circadian rhythm, aging, angiogenesis and response to drug (biological process), endoplasmic reticulum lumen (cellular component), and protein binding (molecular function). As a result, eight genes (JUN, SERPINE1, GINS2, TYMS, HMMR, IGFBP2, BIRC3, TNFRSF12A) were identified as hub genes. Finally, three genes were found significantly changed in both the validation dataset and the mouse model.Conclusion: Our research discovered genes that have the potential to mediate the process of NASH and might be useful diagnostic biomarkers for the disorder.

ObjectiveHealth dietary pattern is related with reduced risk of chronic metabolic disease, but the benefits were not fully clear in the Chinese population. The aim of this study was to explore the association between dietary patterns and multiple chronic metabolic diseases in middle-aged and elderly Chinese.MethodsA total of 718 Chinese adults aged ≥ 45 who lived in the Huairou regions of Beijing were included in the present cross-sectional analysis from 2019 to 2020. Dietary data were obtained by food frequency questionnaires (FFQs). Dietary patterns were identified by principal components analysis (PCA). Logistic regression analysis and hierarchical analysis were used to examine the relationship among dietary patterns, health management, and chronic diseases.ResultsFive dietary patterns were discovered in the subjects. The pattern with the higher percentage of energy supply by lipid was a risk factor for hypertension [odds ratio (OR) = 2.067, p = 0.013]. Lower energy intake (OR = 0.512, p = 0.012) and a reasonable ratio of dietary energy supply (OR = 0.506, p = 0.011) were beneficial to diabetes. The substitution of potato for grain might be an effective way of reducing diabetes (OR = 0.372, p < 0.001). The higher intake of high-quality protein was the protective factor for coronary heart disease (CHD; OR = 0.438, p = 0.008). Moderate intervention (OR = 0.185, p = 0.033) and appropriate health education (OR = 0.432, p = 0.016) could greatly subserve the prevention of chronic diseases, especially for hyperlipidemia. Men were more likely to be affected by health education, intervention, and follow-up than women. The prevalence of multimorbidity was higher in women (43.2%) than men (41.5%). The staple food intake and health management were also important factors to prevent multimorbidity.ConclusionDietary pattern with appropriate energy intake, a reasonable source of energy supply, high quality of macronutrients, and moderate management was associated with decreased risk of chronic metabolic diseases. Further studies are needed to clarify the cause–effect relationship between dietary patterns, health management, and chronic diseases and give suggestions to chronic metabolic disease prevention in middle-aged and elderly people in a rural area.

Under a persistent warming climate and increasing human activities, permafrost in the Source Area of the Yellow River (SAYR) has been degrading regionally, resulting in many eco-environmental problems. This paper reviews the changes in air temperature and precipitation over the past 60 years and presents the distribution and degradation of alpine permafrost in the SAYR. The review is focused on the permafrost degradation–induced changes in hydrology, wetlands, thermokarst lakes, ponds, and vegetation. Mean annual air temperatures have been rising at an average rate of 0.4°C/10a over the past 60 years, while precipitation has increased only slightly (16 mm/10a). Borehole temperature monitoring at the depth of 15 m shows the permafrost warming rates of 0.01–0.21°C/10a in the Headwater Aera of the Yellow River. As a result of permafrost thaw, the amount of surface waters has declined while groundwater storage has increased. Due to permafrost degradation, the supra-permafrost water table lowers gradually, resulting in a reduction in areal extents of wetlands and lakes in the SAYR. We further renamed the concept of the burial depth of the ecologically-safe supra-permafrost water table, the minimum depth of the groundwater table for sustaining the normal growth of alpine grassland vegetation, for the SAYR to describe the relationship between the lowering permafrost table and succeeding alpine vegetation. Furthermore, we recommended more studies focusing on snow cover and carbon stock and emissions related to permafrost degradation under a warming climate. We also advised to timely establish the long-term monitoring networks for the rapidly changing mountain cryosphere, alpine ecology, alpine hydrology, eco-hydrology, cryo-hydrogeology, and carbon fluxes. Moreover, process-based models should be developed and improved to better simulate and predict the responses of alpine ecosystem changes to the interacting cryospheric and other environmental variables and their ecological and ecohydrological impacts in the SAYR and downstream Yellow River basins. This study can help better manage the ecological and hydrological environments in the Upper Yellow River that are sensitive to changes in the alpine climate and cryosphere.

Carbon storage is an important component of ecosystem services. Under climate warming and human activities, land use/land cover (LULC) have been undergoing tremendous change, leading to spatio-temporal variations in carbon storage. Based on seven series of LULC data and combined with carbon module of Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) model, spatial-temporal changes in LULC types and carbon storage were analyzed and estimated for Heilongjiang Province, Northeast China. Results show varied carbon storage among different types of LULC. Forest and cropland are the dominant LULC types in Heilongjiang Province, Northeast China, accounting for 46–49% (20.90 × 104–22.12 × 104 km2) and 30–37% (13.56 × 104–16.70 × 104 km2) of the total area. Areal extents of forest, grassland, and unused land declined from 1980 to 2015, by 1.22, 0.84, and 1.11 × 104 km2, respectively; while those of cropland and construction land expanded, by 3.14 and 0.08 × 104 km2, respectively. From 1980 to 2015, carbon storage displayed consistent change trends with those of LULC types: carbon storage of forest, grassland, and unused land decreased by 236.22, 116.61 and 21.82 × 106 Mg C, respectively; and those of cropland and construction land increased by 414.65 and 0.99 × 106 Mg C, respectively. The total carbon storage in the study region was 6,863.06 × 106–6,907.64 × 106 Mg C, for which the forest, cropland, and grassland were the major contributor (6,778.75 × 106–6,840.57 × 106 Mg C). Due to the conversion of large extents of forest, grassland, and unused land to cropland, which facilitated the formation of carbon sinks and thus enlarged the carbon storage by 45.36 × 106 Mg C from 1980 to 2015. Frequent forest fires, urban expansion, farmland reclamation, and engineering construction were the important factors of changes in the LULC, accelerating permafrost degradation and leading to obvious changes in the total carbon storage in the Heilongjiang Province, Northeast China. Therefore, the estimation of carbon storage in different LULC types can provide important data support and have important implications for evaluation of ecosystem services and carbon cycle.

This study aims to determine the genetic structure of rainbow clam Moerella iridescens in different sea areas of China. Seventeen pairs of microsatellite primers (SSR) were used to amplify the SSRs of rainbow clam in Lianyungang of Haizhou Bay, Chongming of Shanghai, Ningde of Fujian, Daishan of Zhoushan, and Cixi and Wenzhou of Zhejiang. A total of 1,146 alleles were detected in 310 individuals from the 17 SSR loci. The average observed heterozygosity of six populations was 0.4381−0.6139, the average expected heterozygosity was 0.5897−0.7325, and the average Shannon diversity index was 1.2655−1.7998. The clams exhibited rich genetic diversity, and the FST of the genetic differentiation index of the six populations was 0.0470, indicating low genetic differentiation among the populations. The results indicated that rainbow clams along the coasts of China exhibited high diversity and low population differentiation.

Psoriatic arthritis (PsA) is a chronic inflammatory joint disease, and the diagnosis is quite difficult due to the unavailability of reliable clinical markers. This study aimed to investigate the fecal metabolites in PsA by comparison with rheumatoid arthritis (RA), and to identify potential diagnostic biomarkers for PsA. The metabolic profiles of the fecal samples from 27 PsA and 29 RA patients and also 36 healthy controls (HCs) were performed on ultra-high-performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). And differentially altered metabolites were screened and assessed using multivariate analysis for exploring the potential biomarkers of PsA. The results showed that 154 fecal metabolites were significantly altered in PsA patients when compared with HCs, and 45 metabolites were different when compared with RA patients. A total of 14 common differential metabolites could be defined as candidate biomarkers. Furthermore, a support vector machines (SVM) model was performed to distinguish PsA from RA patients and HCs, and 5 fecal metabolites, namely, α/β-turmerone, glycerol 1-hexadecanoate, dihydrosphingosine, pantothenic acid and glutamine, were determined as biomarkers for PsA. Through the metabolic pathways analysis, we found that the abnormality of amino acid metabolism, bile acid metabolism and lipid metabolism might contribute to the occurrence and development of PsA. In summary, our research provided ideas for the early diagnosis and treatment of PsA by identifying fecal biomarkers and analyzing metabolic pathways.

As a DNA receptor, cyclic GMP-AMP synthase (cGAS) plays a crucial role in the immune system by recognizing abnormal DNA in the cytoplasm and activating the stimulator of interferon genes (STING) signaling pathway. This signaling cascade reaction leads to an immune response produced by type I interferon and other immune mediators. Recent advances in research have enhanced our current understanding of the potential role of the cGAS/STING pathway in anticancer therapy; however, in some cases, chronic STING activation may promote tumorigenesis. The present review article discusses the biological mechanisms of the cGAS/STING pathway, its dichotomous role in tumors, and the latest advances with respect to STING agonists and antagonists.

Background: The Chinese Neonatal Network (CHNN) is a nationwide neonatal network that aims to improve clinical neonatal care quality and short- and long-term health outcomes of infants. This study aims to assess the quality of the Chinese Neonatal Network database by conducting an internal audit of data extraction.Methods: A data audit was performed by independently replicating the data collection and entry process in all 58 tertiary neonatal intensive care units (NICU) participating in the CHNN. Eighty-eight data elements selected for re-abstraction were classified into three categories (critical, important, less important), and agreement rates for original and re-abstracted data were predefined. Three to five records were randomly selected at each site for re-abstraction, including one short- (0–7 days), two medium- (8–28 days), and two long-stay (more than 28 days) cases. Agreement rates for each data item were calculated for individual NICUs and across the network, respectively.Results: A total of 283 cases and 24,904 data fields were re-abstracted. The agreement rates for original and re-abstracted data elements were 96.1% overall, and 97.2, 94.3, and 96.6% for critical, important, and less important data elements, respectively. Individual site variation for discrepancies ranged between 0.0 and 18.4% for all collected data elements.Conclusion: The completeness, precision, and quality of data in the CHNN database are high, providing assurance for multipurpose use, including health service evaluation, quality improvement, clinical trials, and other research.

Immune checkpoint inhibitors (ICIs) have changed the landscape of cancer treatment and are emerging as promising curative treatments in different type of cancers. However, only a small proportion of patients have benefited from ICIs and there is an urgent need to find robust biomarkers for individualized immunotherapy and to explore the causes of immunotherapy resistance. In this article, we review the roles of immune cells in the tumor microenvironment (TME) and discuss the effects of ICIs on these cell populations. We discuss the potential of the functional interaction between the TME and cancer cells as a predictive biomarker for ICIs. Furthermore, we outline the potential personalized strategies to improve the effectiveness of ICIs with precision.

The aim is to comprehensively and accurately assess potential relationships between single nucleotide polymorphisms (SNP) and lung cancer (LC) risk by summarizing the evidence in systematic reviews and meta-analyses. This umbrella review was registered with the PROSPERO international prospective register of systematic reviews under registration number CRD42020204685. The PubMed, Web of Science, and Embase databases were searched to identify eligible systematic reviews and meta-analyses from inception to August 14, 2020. The evaluation of cumulative evidence was conducted for associations with nominally statistical significance based on the Venice criteria and false positive report probability (FPRP). This umbrella review finally included 120 articles of a total of 190 SNP. The median number of studies and sample size included in the meta-analyses were five (range, 3–52) and 4 389 (range, 354–256 490), respectively. A total of 85 SNP (in 218 genetic models) were nominally statistically associated with LC risk. Based on the Venice criteria and FPRP, 13 SNP (in 22 genetic models), 47 SNP (in 99 genetic models), and 55 SNP (in 94 genetic models) had strong, moderate, and weak cumulative evidence of associations with LC risk, respectively. In conclusion, this umbrella review indicated that only 13 SNP (of 11 genes and one miRNA) were strongly correlated to LC risk. These findings can serve as a general and helpful reference for further genetic studies.

PurposeWe retrospectively analyzed the oncological outcomes of T3 or G3 distal ureteral urothelial carcinoma (DUUC) underwent partial ureterectomy (PU) followed by adjuvant radiotherapy (ART).MethodsFrom January 2008 to September 2019, clinical data from a total of 221 patients with pathologic T3 or G3 who underwent PU or RNU at our hospital were analyzed. 17 patients of them were treated with PU+ART, 72 with PU alone and 132 with radical nephroureterectomy (RNU). Clinicopathologic outcomes were evaluated. Survival was assessed using the Kaplan-Meier method. Cox regression addressed recurrence-free survival (RFS), metastasis-free survival (MFS), cancer specific survival (CSS) and overall survival (OS).ResultsMedian age and follow-up time were 68 (IQR 62-76) years old and 43 (IQR 28-67) months, respectively. In univariate and multivariable analyses, no lymph node metastasis(LNM) and ART were independent prognostic factors of RFS (p=0.031 and 0.016, respectively). ART significantly improved 5-year RFS compared with the PU alone, (67.6% vs. 39.5%, HR: 2.431, 95%CI 1.210-4.883, p=0.039). There was no statistical difference in 5-year RFS between PU+ART and RNU groups (67.6% vs. 64.4%, HR=1.113, 95%CI 0.457-2.712, p=0.821). Compared with PU alone or RNU, PU+ART demonstrated no statistical difference in 5-year MFS (PU+ART 73.2%, PU 57.2%, RNU69.4%), CSS (70.7%, 55.1%, 76.6%, respectively), and OS (70.7%, 54.1%, 69.2%, respectively).ConclusionsFor distal ureteral urothelial carcinoma patients with T3 or G3, adjuvant radiotherapy could significantly improve recurrence-free survival compared with partial ureterectomy alone. There was no significant difference between survival outcomes of PU+ART and radical nephroureterectomy.

Prader–Willi syndrome (PWS) is a complex genetic syndrome caused by the loss of function of genes in 15q11-q13 that are subject to regulation by genomic imprinting and expressed from the paternal allele only. The main clinical features of PWS patients are hypotonia during the neonatal and infantile stages, accompanied by delayed neuropsychomotor development, hyperphagia, obesity, hypogonadism, short stature, small hands and feet, mental disabilities, and behavioral problems. However, PWS has a clinical overlap with other disorders, especially those with other gene variations or chromosomal imbalances but sharing part of the similar clinical manifestations with PWS, which are sometimes referred to as Prader–Willi syndrome-like (PWS-like) disorders. Furthermore, it is worth mentioning that significant obesity as a consequence of hyperphagia in PWS usually develops between the ages of 1 and 6 years, which makes early diagnosis difficult. Thus, PWS is often not clinically recognized in infants and, on the other hand, may be wrongly suspected in obese and intellectually disabled patients. Therefore, an accurate investigation is necessary to differentiate classical PWS from PWS-like phenotypes, which is imperative for further treatment. For PWS, it is usually sporadic, and very rare family history and affected siblings have been described. Here, we report the clinical and molecular findings in a three-generation family with a novel 550-kb microdeletion affecting the chromosome 15 imprinting center (IC). Overall, the present study finds that the symptoms of our patient are somewhat different from those of typical PWS cases diagnosed and given treatment in our hospital. The familial occurrence and clinical features were challenging to our diagnostic strategy. The microdeletion included a region within the complex small nuclear ribonucleoprotein polypeptide protein N (SNRPN) gene locus encompassing the PWS IC and was identified by using a variety of techniques. Haplotype studies suggest that the IC microdeletion was vertically transmitted from an unaffected paternal grandmother to an unaffected father and then caused PWS in two sibling grandchildren when the IC microdeletion was inherited paternally. Based on the results of our study, preimplantation genetic diagnosis (PGD) was applied successfully to exclude imprinting deficiency in preimplantation embryos before transfer into the mother’s uterus. Our study may be especially instructive regarding accurate diagnosis, differential diagnosis, genetic counseling, and PGD for familial PWS patients.

PurposeThe aim of this retrospective study was to probe into clinicopathological features and prognosis of early-onset gastric cancer (EOGC) patients aged ≤ 45 years old.MethodsThis study selected 154 young gastric cancer patients aged ≤ 45 years old and 158 elderly gastric cancer patients aged > 50 years old admitted to West China Hospital of Sichuan University in 2009-2019 as the research object. These patients were further divided into two groups according to whether tumor can be resected radically. The following parameters were analyzed: age, gender, helicobacter pylori (HP) infection status, Her-2 status, pathological type and stage, chemotherapy, tumor differentiation degree, overall survival (OS).ResultsMore than 3,000 patients with gastric carcinoma were screened, and 154 young gastric cancer patients aged ≤ 45 years old were identified as EOGC. Among them, the number of female patients in EOGC group was significantly higher than that of males, accounting for 63.6%. In addition, EOGC were associated with diffuse Laur´en type and poorly differentiated tumors. Interestingly, the Kaplan–Meier method showed that the OS of unresectable EOGC group was significantly lower than that of unresectable LOGC group (P = 0.0005) and chemotherapy containing paclitaxel tended to be more effective in the young people (P = 0.0511). Nevertheless, there was no significant difference in OS between young and elderly patients with gastric cancer in the radical resection group (P = 0.3881).ConclusionEOGC patients have a worse prognosis than late-onset gastric cancer (LOGC) patients with advanced unresectable gastric cancer. Palliative surgery or chemotherapy containing paclitaxel may improve the OS of unresectable young individuals with gastric cancer. Additional randomized controlled trials are required for guiding clinical practice.

Many epidemiological studies have confirmed that ICAM-1 gene single-nucleotide polymorphisms (SNPs) are associated with susceptibility of various cancers, but there are relatively few studies on the relationship between ICAM-1 gene polymorphisms and the risk of cervical cancer. Therefore, we aimed to explore the potential role of ICAM-1 gene polymorphisms and the combined effect of SNPs in the pathogenesis of cervical cancer in Han women in northern China. This case–control group includes 488 cases of cervical cancer, 684 cases of cervical precancerous lesions, and 510 healthy females. Multiplex polymerase chain reaction (PCR) combined with the next-generation sequencing method was used for the determination of gene polymorphisms (rs5498, rs3093030, and rs281432). In our study, we divide cervical cancer into two subgroups: cervical squamous cell carcinoma (CSCC) group and cervical adenocarcinoma (CAC) group. We analyzed the alleles and genotypes of all research subjects using multivariate logistic regression analysis combined with 10,000 permutation tests. In addition, we also analyzed the distribution of haplotypes of the three SNPs in cervical cancer and cervical precancerous lesions. We found that the T allele and the dominant model of rs3093030 were associated with the susceptibility of cervical cancer (p = 0.042, p = 0.040, respectively). However, the significance disappeared after the Bonferroni correction for multiple testing (p > 0.05). For rs5498, its mutant gene G, the codominant model, and the dominant model could reduce the risk of CAC (p = 0.009, p = 0.028, p = 0.011, respectively). Significant differences remained after Bonferroni correction (p < 0.05, all). In addition, the frequency of haplotype “CTG” was significantly lower in the CAC group than in the controls. In conclusion, the study suggested that ICAM-1 gene polymorphisms may have a potential role in the pathogenesis of cervical cancer in the northern Chinese Han population.

Mastitis, an inflammatory disease, causes severe economic loss in the dairy industry, which is mainly infected by bacteria. Staphylococcus aureus (S. aureus), the major pathogenic microorganism, derived from lipoteichoic acid (LTA) has been identified to activate inflammatory responses, but the cellular or intercellular regulatory mechanism is unclear. This study mainly focused on the effects of LTA in bovine mammary epithelial cells (Mac-T) and elaborated the regulation of microRNAs (miRNAs). The results showed that LTA enhanced the messenger RNA (mRNA) expression and production of tumor necrosis factor α (TNF-α) and interleukin (IL)-6. Furthermore, LTA could activate Toll-like receptor (TLR)2/MyD88-mediated phosphoinositide 3-kinase (PI3K)/AKT pathway, and TLR2 plays a pivotal role in LTA-induced inflammatory responses. The results of qRT-PCR showed that miRNA levels increased and reached the highest at 3 h and then gradually decreased over time in Mac-T cells. In exosomes, the levels of 11 and three miRNAs were upregulated and downregulated at 24 h, respectively. In addition, miR-23a showed the highest increase in Mac-T cells treated with LTA and targeted PI3K to regulate inflammatory responses. Furthermore, Mac-T cell-derived exosomes were identified to play a cell–cell communication by promoting M1 polarization of bovine macrophages. In summary, our study demonstrated that LTA could activate inflammatory responses via TLR2/MyD88/PI3K/AKT signaling pathway, and miR-23a inhibited it by targeting PI3K. Furthermore, we found that Mac-T cell-derived exosomes might be associated with inflammatory responses by promoting M1 polarization of bovine macrophages.

Objective: To describe cardiovascular pharmacological support in infants born at 3 days. Prolonged cardiovascular pharmacological support (>3 days) was independently associated with lower rates of survival without morbidity in very-low-birth-weight infants, compared with infants with shorter durations. Dopamine was the most commonly used cardiovascular agent. The cardiovascular pharmacological support rates varied from 1.9 to 65.8% among the participating NICUs.Conclusions: The rate of cardiovascular pharmacological support within the first postnatal week was high with prolonged durations in Chinese NICUs. Marked variation in cardiovascular support existed among participating NICUs. Cardiovascular pharmacological support during the early postnatal period, especially prolonged, may be associated with adverse neonatal outcomes.Clinical Trial Registration: The original trial was registered as “Reduction of Infection in Neonatal Intensive Care Units using the Evidence-based Practice for Improving Quality” (ID: NCT02600195) on clinicaltrials.gov. https://clinicaltrials.gov/ct2/show/NCT02600195?term=NCT02600195&draw=2&rank=1.

Over the past decade, immune checkpoint blockade (ICB) therapy has revolutionized the outlook for oncology with significant and sustained improvement in the overall patient survival. Unlike traditional cancer therapies, which target the cancer cells directly, ICB acts on the immune system to enhance anti-tumoral immunity. However, the response rate is still far from satisfactory and most patients are refractory to such treatment. Unfortunately, the mechanisms underlying such heterogeneous responses between patients to ICB therapy remain unclear. In addition, escalating costs of cancer care and unnecessary immune-related adverse events also are pertinent considerations with applications of ICB. Given these issues, identifying explicit predictive biomarkers for patient selection is an urgent unmet need to increase the efficacy of ICB therapy. The markers can be classified as tumor related and non-tumor-related biomarkers. Although substantial efforts have been put into investigating various biomarkers, none of them has been found to be sufficient for effectively stratifying patients who may benefit from immunotherapy. The present write up is an attempt to review the various emerging clinically relevant biomarkers affecting the efficacy of immune checkpoint inhibitors, as well as the limitations associated with their clinical application.

In recent years, as our understanding of tumor immunology is continuously improved, immunotherapy has come to the center stage of cancer therapy and is deemed as the most promising approach for cancer control. Although immunotherapy, particularly immune checkpoint blockade (ICB), has achieved a milestone in several types of tumors, the majority of cancer patients do not benefit from immunotherapy. The dismal outcome of cancer immunotherapy is mainly due to primary or acquired resistance arising from tumor immune evasion. Exploring the mechanisms of tumor immune evasion in the course of immunotherapy may identify biological targets to conquer tumor resistance to immunotherapy. In this review, we highlight tumor cell-intrinsic and -extrinsic factors that may underlie tumor resistance to immune checkpoint blockers. Targeting these factors in combination with immune checkpoint blockers points to the future direction of cancer immunotherapy.